HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 51, No. 1, 1999
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■ Alkenyl-substituted N,N''-Dioxygenated Pyrazoles by Nitrosation of Dienone Oximes
John F. Hansen* and Jinlin Wang
*Department of Chemistry, 305 Felmeley Hall, Campus Box 4160, Illinois State University, Normal, Illinois 61790-4160, U.S.A.
Abstract
Nitrosation of 2,6-dirnethyl-2,5-heptadien-4-one oxime gave 3,3-dimethyl-5-(2-methyl-1-propenyl)-3H-pyazole 1,2-dioxide, while 1,5-diphenyl-1,4-pentadien-3-one oxime gave 3(5)-phenyl-5(3)-styryl-1-hydroxypyrazole 2-oxide. The latter pyrazole could also be obtained in low yield by nitrosation of 1,5-diphenyl-2,4-pentadien-1-one oxirne.
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■ Design and Synthesis of 1,4-Diazabicyclo[4.3.0]nonane Peptidomimetic Endothelin Antagonists
Ming Fai Chan,* Bore G. Raju, Adam Kois, Jay I. Varughese, Kottayil I. Varughese, and Vitukudi N. Balaji
*Palomar Research, Inc., 6353 El Camino Real, Suite D, Carlsbad, California 92009-1607, U.S.A.
Abstract
The design and synthesis of a series of 2-(3-indolylmethyl)-4-(tert-butoxycarbonyl)-1,4-diaza-2-oxobicyclo[4.3.0]nonane-9-carboxylc acid peptidomimetics based on the peptide endothelin antagonists BQ-123 and FR139317 were described. The stereochemistry of the active (3R,6S,9R) isomer was determined by X-Ray crystallography.
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■ An Improved Synthesis of the ABC Ring Model of Ecteinascidins
Naoki Saito, Hiroshi Kamayachi, Masashi Tachi, and Akinori Kubo*
*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
An improved synthesis of 1,2,3,4,5,6-hexahydro-1,5-imino-9-methoxy-3,8,11-trimethyl-4-oxo-3-benzazocine (6) as an ABC ring model compound of ecteinascidins from 3-(4-methoxy-3-methylphenylmethyl)-1-methyl-2,5-piperazinedione 3 is described.
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■ Synthesis and Cyclization of Novel Lumazine - Enediyne Chimeras
Nakyen Choy and Keith C. Russell*
*Department of Chemistry, College of Arts of Sciences, University of Miami, 1301 Memorial Dr., Coral Gables, FL 33124-0431, U. S. A.
Abstract
Lumazine derivatives (6-8), appended with ethynyl groups in positions 7 and 8, were synthesized and examined for their ability to undergo Bergman cyclization. Oxo compound (7) was found to give good yields of Bergman cyclization products (~ 37 %), whereas the analogues (6) and (8) did not cyclize as efficiently or gave no identifiable cyclization products.
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■ Reaction of 2-Benzoselenopyrylium Salts with Nucleophiles: Formation of 1-Functionalized Isoselenochromenes
Haruki Sashida* and Kazuo Ohyanagi
*School of Pharmacy, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan
Abstract
1-Unsubstituted isoselenochromenes (3) were converted into the 2-benzoselenopyrylium salts (4) by treatment with Ph3C+ BF4- and the reaction of the salts (4) with several nucleophilic reagents (alcohol, amine, cyanide, acetone, and Grignard reagents) afforded the corresponding 1-functionalized isoselenochromenes (5-9) in high yields, respectively. 1-Alkyl- and 1-phenyl-2-benzoselenopyrylium salts (10) were also obtained from 9.
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■ Synthesis of Decahydroacridines under Microwaves Using Ammonium Acetate Supported on Alumina
Margarita Suárez,* André Loupy,* Esperanza Salfrán, Lourdes Morán, and Emilio Rolando
*Laboratoire des Réactions Sélectives sur Supports, CNRS UA 478, Institut de Chimie Moleculaire d'Orsay, Université de Paris-Sud, Batiment 410, 91405 Orsay Cedex, France
Abstract
Acridine derivatives have been synthesized under microwave irradiation under solvent-free conditions using ammonium acetate supported on neutral or basic alumina and catalytic N,N-dimethylforrnamide. The obtained results show high yields. The specific "non thermal" effect produced by microwave irradiation has been demonstrated.
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■ A Mild Method for the Preparation of 8-Substituted Xanthines from 5,6-Diaminouracils
Aline D. de Araujo, Edmond Bacher, F. W. Joachim Demnitz,* and Douglas A. Santos
*Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade UniversitÁria, CEP 50.670-901, Recife - PE, Brazil
Abstract
The Schiff base derivatives (3), prepared from the respective 5,6-diaminouracil (1) and aldehydes can be mildly oxidatively cyclized with m-CPBA in MeCN to afford C-8 substituted xanthines (6).
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■ Stereoselective Synthesis of Enantiomerically Pure Isoxa-zolidine-fused δ-Lactams
Ugo Chiacchio,* Antonino Corsaro, Anna Piperno, Antonio Rescifina, Giovanni Romeo, and Roberto Romeo
*Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy
Abstract
Enantiomerically pure isoxazolidine-fused δ-lactams have been obtained by intramolecular nitrone cycloaddition starting from homochiral amido aldehydes. The stereocenter of the homochiral precursor controls the stereochemical course of the process.
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■ Catalytic Thione-Thiol Rearrangement of Xanthates by 4-Dialkylaminopyridine
Hidetoshi Nakagawa, Masashi Eto, and Kazunobu Harano*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
Pyridines bearing electron-donating substituents are useful catalysts for the rearrangement of O,S-dialkyl xanthates (1) to S,S-dialkyl dithiocarbonates (2). The rearrangement was analyzed by semiempirical and ab initio molecular orbital methods. The transition-structure analyses indicate that the pyridine-ring nitrogen of dialkylarninopyridine rather than the dialkylamino nitrogen attacks the O-alkyl carbon of xanthates. The reaction proceeds through an SN2 mechanism to give the dithiolcarbonate anion (RSCOS-) which acts as an actual catalyst.
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■ Regioselective Synthesis of 1H-2-Benzoselenopyrans. Reaction of 4,4'-Dimethoxyselenobenzophenone with Acetylenes
Kentaro Okuma,* Yuji Koga, Yayoi Furunushi, Kazuki Kojima, and Kosei Shioji
*Faculty of Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Abstract
4,4’-Dimethoxyselenobenzophenone combines as a diene with methyl propiolate, ethyl propiolate, and phenylacetylene producing 1H-2-benzoselenopyrans; the primary [4+2] cycloaddition is followed by 1,3-prototropy. This reaction proceeds regioselectively. On the other hand, a nonaromatic ketone was obtained by using propiolic acid as the substrate.
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■ Four New 4-Phenylcoumarins from Calophyllum dispar. Isolation and Hemisynthesis
David Guilet, Cécile Morel, Nathalie Noyer, Maryse Cornec, Denis Séraphin, Christian Wiart, A. Hamid A. Hadi, Thierry Sévenet, Pascal Richomme,* and Jean Bruneton
*U.F.R. des Sciences Medicales et Pharmaceutiques et Ingénierie de la Santé, SONAS, Université d'Angers, 16, Bd Daviers, F-49100 Angers, France
Abstract
Four new 4-phenylcoumarins, disparinols A and B, isodisparinols A and B, having a 2-hydroxy-3-methylbut-3-enyl substituent were isolated from the bark of Calophyllum dispar (Clusiaceae). Their structures were established by means of spectroscopic studies and confirmed by hemisynthesis.
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■ Isolation, Conformational Analysis and X-Ray Structure Determination of a Trifluoromethyl-stabilized Hexahydropyrimidine — An Intermediate in the
Biginelli Reaction
C. Oliver Kappe,* S. Fabio Falsone, Walter M. F. Fabian, and Ferdinand Belaj
*Institute of Organic Chemistry, Karl-Franzens-University Graz, Heinrichstr. 28, A-8010 Graz, Austria
Abstract
Hexahydropyrimidine-5-carboxylic acid ethyl ester (8) was obtained from Biginelli-type condensation of ethyl trifluoroacetoacetate with urea and benz-aldehyde. The conformational features of this hexahydropyrimidine were investigated by computational and X-Ray crystallographic studies. The geometries of the four possible diastereoisomers were fully optimized using semiempirical (AM1, AM1/MM) methods. The structure of the thermodynamically most stable diastereoisomer was further studied by ab initio (HF/3-21G) methods.
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■ Oxazepines and Thiazepines, 36. Diastereoselective Sulfoxidation of 2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones by Dimethyldioxirane
Tamás Patonay,* Waldemar Adam,* József Jeko, Katalin E. Kövér, Albert Lévai, Márta Németh, and Karl Peters
*Department of Organic Chemistry, Lajos Kossuth University, H-4010 Debrecen, P.O.Box 20, Hungary
Abstract
The highly chemoselective dimethyldioxirane oxidation of 2-substituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-one (1) allows the synthesis of the corresponding sulfoxides (2) or sulfones (3) in good yields. The relative stereochemistry of the sulfoxides has been unequivocally determined by X-Ray and NMR methods. The high trans diastereoselectivity can be explained on the basis of steric control.
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■ Reactions of 4-Acetylsydnones with Hydrazine: Formation of 2,4-Dihydropyrol-3-ones
Hsien-Ju Tien,* Shaw-Tao Lin,* and Mei-Lin Yang
*Department of Applied Chemistry, Providence University, 200 Chungchi Road, Sha-Lu, Taichung Hsien, 433, Taiwan, R.O.C.
Abstract
Reactions of 4-acetylsydnones with hydrazine at room temperature yielded a series of 2,4-dihydropyrazol-3-ones. The cycloaddition via sydnone rings with loss of a nitrogen oxide ion is a new type of reaction for the application of sydnone in organic synthesis.
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■ A Novel Synthesis of Isoquinolines Containing an Electron Withdrawing Substituent
Harumichi Kohno and Koichiro Yamada*
*Medicinal Chemistry Research Laboratory, Tanabe Seiyaku Co.Ltd.,, 2-2-50, Kawagishi, Toddda, Saitama 335-8505, Japan
Abstract
3,4-Dihydroisoquinolines (10, 13) and isoquinolines (11), having various electron withdrawing substituent were synthesized in two steps from N-benzenesulfonyl- or N,N-dimethylsulfamoyl-β-phenethylamines (2 and 5). A novel cyclization method using ethyl chloro(methylthio)acetate (1) in the presence of SnCl4 as Lewis acid, followed by acid or base treatment provides the title compounds in good yield.
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■ A Synthesis of Some Trimethoxylated 1,2,3,4-Tetrahydroisoquinoline Alkaloids via Pummerer Reaction of N-Trimethoxybenzyl-N-[2-(phenyl-
sulfinyl)ethyl]formamides
Tatsumi Shinohara, Akira Takeda, Jun Toda, Michiyo Kohno, and Takehiro Sano*
*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
Pummerer reaction of N-trimethoxybenzyl-N-[2-(phenylsulfinyl)ethyl]formamides (7) gave N-formyl-1,2,3,4-tetrahydro-4-phenyl-sulfanylisoquinolines (9) which were converted into trimethoxylated 1,2,3,4-tetrahydroisoquinoline alkaloids in the family of Cactaceae, formylanhalinine (10a), nortehaunine (12a), anhalinine (12b), and tehaunine (13a).
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■ Ring Contraction of 3-Carboxamide or 3-Carboxylate of 4-Hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide and Analogous 1(2H)-Isoquinolinone-3-carboxylate
Ali Khalaj* and Neda Adibpour
*Department of Medicinal Chemistry, College of Pharmacy, Tehran Medical Sciences University, P.O.Box 14155-6451, Tehran, Iran
Abstract
A novel ring transformation of 3-carboxylate or 3-carboxamide of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide and analogous 1(2H)-iso-quinolinone-3-carboxylate to the 5-membered rings upon the reaction with carbonyl compounds in the presence of primary or secondary amines is described.
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■ A Convenient Synthesis of Polyfunctionally Substituted 2',2'-Bis(ethoxycarbonyl)methylene-5'-methoxycarbonyl(cyano)spiro[dihydroacridine-9(10H),4'-thiazolidines]
Juraj Bernát, Igor Chomca, Pavol Kristian,* Kalevi Pihlaja, Karel Douglas Klika, and Ján Imrich
*Department of Organic Chemistry, P. J. SafÁrik University, Moyzesova 11, SK-04167 Kosice, Slovakia
Abstract
2-(Acridin-9-ylthiocarbamoyl)malonic acid diethyl esters (2a-c) obtained via reaction of isothiocyanatoacridines (1a-c) with sodium diethyl malonate afforded with methyl bromoacetate (bromoacetonitrile) non-isolable S-alkylated intermediates (3a-f), which cyclized in alkaline medium to 2’,2’-bis(ethoxycarbonyl)methylene-5’-methoxycarbonyl(cyano)spiro[dihydroacridine-9(10H),4’-thiazolidines] (4a-f).
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■ Photochemistries of Oxadiazabicyclo[1.2.4]nonadiene, Oxadiazabicyclo[2.2.3]nonadiene, and Oxatriazabicyclo[2.2.3]nonadiene Systems: Cycloreversion Reactions to Generate Azepine or Diazepine Derivatives and Isomerization Reaction of Oxadiazabicyclo[2.2.3]nonadiene Systme to Oxadiazabicyclo[1.2.4]nonadiene System
Tsunetaka Tomita, Hiroyuki Ishiguro, and Katsuhiro Saito*
*Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Abstract
An irradiation of an oxadiazabicyclo[1.2.4]nonadiene derivative in acetonitrile with a low pressure mercury lamp afforded an 1H-azepine derivative. An irradiation of an oxadiazabicyclo[2.2.3]nonacliene derivative gave an oxadiazabicyclo[1.2.4]nonadiene derivative and an 1H-azepine derivative. On the other hand, a photo-reaction of an oxatriaza-bicyclo [2.2.3]nonadiene derivative generated a 1H-1,2-diazepine derivative. All these reactions are considered to proceed through the same type of reaction intermediate.
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■ CMR Spectra of N-Oxygenated Pyrazoles. I. 3,5-Dialkyl- and 3-Alkyl-5-phenyl-4-oxo-4H-pyrazole 1,2-Dioxides
Wayne E. Zeller,* Lynn S. Zeller, and John F. Hansen*
*Department of Chemistry, 305 Felmeley Hall, Campus Box 4160, Illinois State University, Normal, Illinois 61790-4160, U.S.A.
Abstract
The 13C NMR spectra of a series of 3,5-dialkyl- and 3-alkyl-5-phenyl-4-oxo-4H-pyrazole 1,2-dioxides were determined. Signals for the carbonyl carbon, C4 of the pyrazole, appeared at δ 186.2 to 188.1 ppm, while the C3 and C5 signals were found in the region of 105.8 to 112.8 ppm. The effect of structural variation of the alkyl groups on the chemical shift of C3 in a selected series of these compounds was investigated using published electronic and steric parameters. Strong correlations were observed with electronic parameter sets σ* and Eσ when augmented with a variety of published steric parameter sets.
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■ An SNAr-based Preparation of 1-(2-, 3-, and 4-Pyridyl)indoles Using Potassium Fluoride/Alumina
William J. Smith III and J. Scott Sawyer*
*Lilly Reserach Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285-4813, U.S.A.
Abstract
The reaction of indole with 2-, 3-, and 4-halopyridines in the presence of potassium fluoride/alumina and 18-crown-6 in DMSO at 120 °C is effective in producing 1-(2-, 3-, and 4-pyridyl)indoles in moderate to good yields.
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■ Synthesis of 1,2,4-Triazolo[5,1-b]-1,3,5-thiadiazepin-5-ylamine Derivatives
Choong Eui Song,* Ji-Sook Kim, Jung Hoon Choi, and Byung Woo Jin
*Division of Applied Science, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea
Abstract
1,2,4-Triazolo[5,1-b]1,3,5-thiadiazepin-5-ylamine derivatives were synthesized by the reaction of N-[2-(1,2,4-triazol-5-ylthio)phenyl]thioureas with DCC via cyclodesufurization.
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■ Preparation and Hydrolysis of 3-Alkoxy-5-amino-4,6-dicyano-1,8,8-trimethyl-2-azabicyclo[2.2.2]octa-2,5-dienes
Yoshiharu Nakano,* Yoshitaka Kaneko, and Wu Ai Fen
*Faculty of Science, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512, Japan
Abstract
Solid base catalyzed condensation reaction of acetone with malononitrile in alcohol gave 3-alkoxy-5-amino-4,6-dicyano-1,8,8-trimethyl-2-azabicyclo[2.2.2]octa-2,5-dienes. The 2-aza bridge of the compound was cleaved hydrolytically in dilute hydrochloric acid to give 6-carbomethoxy-2,6-dicyano-3,5,5-trimethylcyclohex-2-enone. The compound was further decarbomethoxylated in this conditions to give 2,6-dicyano-3,5,5-trimethylcyclohex-2-enone of which crystal structure was determined by X-Ray diffraction method.
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■ Chelidonic Acid as Precursor for 2,5-Desoxy-C-glycosides
Boris Schmidt
*Institut für Organische Chemie, Universität Hannover, Schneiderberg 1b, D-30167 Hannover, Germany
Abstract
Diethyl chelidonate (1) was converted by 5 convenient steps into the 2,4,6-trifunctionolized tetrahydropyran (6), which is a key intermediate for natural products and peptide turn mimetics. The important all syn-configuration was achieved by catalytic hydrogenation.
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■ A Cautionary Note on the Use of Commercial (R)-MTPA-Cl and (S)-MTPA-Cl in Determination of Absolute Configuration by Mosher Ester Analysis
Balawant S. Joshi* and S. William Pelletier
*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.
Abstract
While the absolute configuration of a Mosher ester derivative (MTPAOR) is identical with that of the Mosher acid (MTPAOH) precursor, it is opposite that of the Mosher acid chloride (MTPA-Cl). Since (R)-MTPA-Cl and (S)-MTPA-Cl are now commercially available, incorrect conclusions may be drawn in deriving the absolute configuration, if this fact is overlooked. The absolute configuration of (-)-vasicinone (1) derived by Mosher ester analysis (Tetrahedron Asymmetry, 1996, 7, 25) has been revised as 3S. Masher ester analysis of (-)-vasicine (2) confirmed a 3S configuration for this alkloid.
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■ Mechanistic Insight into the Aromatization of Cyclic p-Quinonemethides to Indoles
Tushar A. Kshirsagar* and Laurence H. Hurley
*c/o Business Office PHR 5.114, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712-1074, U.S.A.
Abstract
Two mechanisms have been previously proposed for the aromatization of cyclic p-quinonemethides to indoles. A novel synthetic route to indoles via an unstable cyclic p-quinonemethide has provided additional insight into the mechanism of cyclization. Since this key intermediate lacks the functional groups required for one of the mechanistic pathways (Pathway B), it appears that cyclization occurs via Pathway A.